Expression of enzymes synthesizing (aldehyde dehydrogenase 1 and retinaldehyde dehydrogenase 2) and metabolizing (Cyp26) retinoic acid in the mouse female reproductive system

Vitamin A is required for female reproduction. Rodent uterine cells are abl e to synthesize retinoic acid (RA), the active vitamin A derivative, and ex press RA receptors. Here, we report that two RA-synthesizing enzymes [aldeh yde dehydrogenase 1 (Aldh1) and retinaldehyde dehydrogenase 2 (Raldh2)] and a cytochrome P450 (Cyp26) that metabolizes vitamin A and RA into more pola r metabolites exhibit dynamic expression patterns in the mouse uterus, both during the ovarian cycle and during early pregnancy. Aldh1 expression is u p-regulated during diestrus and proestrus in the uterine glands, whereas Ra ldh2 is highly induced in the endometrial stroma in metestrus. Cyp26 expres sion, which is not detectable during the normal ovarian cycle, is strongly induced in the uterine luminal epithelium, 24 h after human CG hormonal adm inistration. Raldh2 stromal expression also strongly responds to gonadotrop in (PMSG and human CG) induction. Furthermore, Raldh2 expression can be hor monally induced in stromal cells of the vagina and cervix. All three enzyme s exhibit differential expression profiles during early pregnancy. Aldh1 gl andular expression is sharply induced at 2.5 gestational days, whereas Rald h2 stromal expression increases more steadily until the implantation phase. Cyp26 epithelial expression is strongly induced between 3.5-4.5 gestationa l days, i.e. when the developing blastocysts colonize the uterine lumen. Th ese data suggest a need for precise regulation of RA synthesis and/or metab olism, in both cycling and pregnant uterus.